"The nature of these new genes is not obvious and we wouldn't have guessed their relationship to cancer if we hadn't followed this approach," says Lowe. "They may now allow us to make headway into poorly understood areas of cancer."
The newly identified tumor suppressor genes affect a wide array of cellular activities, including maintenance of cell structure, cellular metabolism, cell proliferation and control of the levels of various tumor growth-enhancing proteins in the cell's nucleus. In one instance, the team's strategy also uncovered not genes in isolation but an entire network of genes that go awry in liver cancer. "Given that the cancer puzzle involves multiple genes in various combinations, we need to find all the hits that make the cell tip over the edge," says Lowe, explaining one advantage of his team's broad strategy.
Some of the genes identified might also lead to new strategies for cancer therapy. For example, some of the newly discovered tumor suppressor genes "code" for proteins that are secreted, which indicates that their ability to prevent cancer is dependent on their presence outside the cell. Reversing the loss of such proteins - by replenishing their levels via injections - is an easier fix than having to correct a defect in the genome via gene therapy.
In other words, the CSHL team's new strategy now makes it possible to rapidly filter from genomic information those genes that specifically impact cancer development in living animals, and thus focus follow-up studies on those that might be most clinically useful.
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